Brooke et al.
, J Aging Geriatr Med 2021, 5:4
Research Article
Anticholinergic Burden and
Hospital Delirium in an
Appalachian University Hospital
1*
Shannon Brooke , Dhar Romika , Bibb Minta , Haghnazar
1 2
Hameed 3 , Navia ROsvaldo 4 and Thompson James
1 for non-psychiatrically trained clinicians. It was validated against the
Abstract
Background: Delirium is a challenging condition in the geriatric
inpatient population due to its multifactorial nature. As anticholinergic
medications have been observed to be associated with delirium,
this association has led to the development of the Anticholinergic
Cognitive Burden scale (ACB). Our objective is to determine whether
a high ACB score is associated with delirium within an Appalachian
population in a West Virginia statewide referral center.
Methods: In this retrospective cross-sectional study, 174 patients
65 years or older were assessed with the Confusion Assessment
Method (CAM) upon arrival to a general medicine unit at J. W. Ruby
Memorial Hospital in Morgantown, West Virginia. The ACB scores
were analyzed with reference to presence of delirium per the CAM.
Subsequently, ACB scores were compared at two time points—
arrival onto the inpatient unit and on the date of discharge.
Results: There was no significant association between increased
ACB score and presence of delirium. There was no difference in
ACB score between patients with and without delirium (p=0.855).
When comparing ACB scores on date of CAM versus on date of
discharge, there was no significant difference between patients with
or without delirium (p=0.467).
Conclusion: There was no significant association between a high
ACB score and a positive CAM at the time of initial assessment
within the limitations of the study. Additionally, there was no change
in anticholinergic burden upon patient discharge based on ACB
scores.
Keywords: Anticholinergic; Delirium; Anticholinergic Cognitive
Burden scale (ACB)
Introduction
Delirium is a challenging condition within geriatric inpatient
populations and is associated with significant morbidity and
mortality. It is a neuropsychiatric syndrome characterized by severe
confusion, decline in cognitive ability, inattentiveness, psychomotor
disturbances, impaired sleep-wake cycle, and/or emotional and
perceptual disturbances [1]. It is estimated that 20% of all hospitalized
patients experience delirium at any one time [2]. When delirium
occurs among hospitalized elderly patients, it can complicate hospital
*Corresponding author: Shannon Brooke, Department of Medicine, West
Virginia University, Morgantown, WV, United States, Tel: +17177985183;
E -mail: brooke. shannon@hsc.wvu.edu
Received date: May 06, 2021; Accepted date: May 20, 2021;
Published date: May 27, 2021
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Journal of Aging and
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course and lead to extended stays, worsening cognitive outcomes,
inappropriate treatments, distress for the patient and family, and
elevated mortality. Additionally, delirium can increase hospital cost by
$2500 per patient and $6.9 billion in hospital costs per year [3].
To diagnose delirium, many tools have been developed for quick
assessment at the bedside. One such tool is the Confusion Assessment
Method (CAM), which is among the most widely used surveys created
Diagnostic and Statistical Manual for Mental Disorders (DSM-V) [4],
the CAM has a sensitivity of 94% and specificity of 89% [5].
Risk factors for delirium include: advanced age, prior cognitive
impairment, dehydration, fracture, infection, polypharmacy,
immobility, restraints, and sensory impairment [6,7].
Prescribed medications have been found to precipitate delirium in
between 12%-39% of cases.8
Anticholinergic drugs have detrimental effects on the aged brain
because of increased permeability of the blood–brain barrier, slower
metabolism and drug elimination, and age-related deficits in central
cholinergic transmission [8,9]. Reduced cerebral acetylcholine has
been hypothesized to be the common final pathway in the development
of delirium in response to inflammation [10].
Hence, in the past few years, research has heavily focused on
an association between anticholinergic medications and cognitive
impairment in older adults. In a 2008 review of thirteen published
longitudinal studies, Boustani et al found that medications with
anticholinergic activity were associated with delirium as well as
decreased cognitive performance in the acute setting [11]. The results
are mixed with regards to relationship between anticholinergic
medications and specifically the timing of the onset of delirium. In a
recent study of hospitalized adults 65 years and older, the authors found
that a higher pre-admission anticholinergic burden was associated
with an increased prevalence of delirium [12].However, other
studies have observed no association be-tween the administration
of anticholinergic medications and the development of delirium in
elderly, cancer, or intensive care patients [13-17]. Contrasting results
may be explained by limitations to the drug scales themselves as well
as population variations.
There are multiple scales for assessing anticholinergic burden
within the contexts of different populations analyzed. The
Anticholinergic Cognitive Burden scale (ACB) was derived in 2008
and validated with other similar scales including those based on
physiologic measurement of serum anticholinergic metabolites as well
as scales developed by expert opinion and cognitive assessments [18].
The ACB scale uses four qualitative scores from 0 to 3 signifying the
effects of anticholinergic use on cognitive impairment. (Tables 1-3)
How’s a list of drugs separated into three categories based on cognitive
burden. The Anticholinergic Burden scale was chosen for this study
as previous studies employing this scale have found an ability to
predict cognitive impairment in older adults[18]. Two additional well
validated scales that are commonly used include the Anticholinergic
Drug Scale as well as the Anticholinergic Risk Scale [18,19]. It is
important to note that there is no defined standard scale for assessing
anticholinergic burden.
 Citation: Brook e S, Dhar R, Bibb M, Hamed H, Navia RO, et al. (2021) Anticholinergic Burden and Hospital Delirium in an Appalachian University Hospital.
J Aging Geriatr Med 5:4.

Table 1: Utility of lignin as a value-added product [13-17]. Molindone Moban™

Generic Name Brand Name Nefopam Nefogesic™
Alimemazine Theralen ™ Oxcarbazepine Trileptal™
Alverine Spasmonal™ Pimozide Orap™
Alprazolam Xanax™ Table 3: Anticholinergic burden scale drugs with ACB score of 3.
Aripiprazole Abilify ™
Generic Name Brand Name
Asenapine Saphris™
Amitriptyline Elavil™
Atenolol Tenormin™
Amoxapine Asendin™
Bupropion Wellbutrin™, Zyban™
Atropine Sal-Tropine™
Captopril Capoten™
Benztropine Cogentin™
Cetirizine Zyrtec ™
Brompheniramine Dimetapp™
Chlorthalidone Diuril™, Hygroton™
Carbinoxamine Histex™, Carbihist™
Cimetidine Tagamet™
Chlorpheniramine Chlor-Trimeton™
Clidinium Librax™
Chlorpromazine Thorazine™
Clorazepate Tranxene™
Clemastine Tavist™
Codeine Contin™
Clomipramine Anafranil ™
Colchicine Colcrys™
Clozapine Clozaril™
Desloratadine Clarinex™
Darifenacin Enablex™
Diazepam Valium™
Desipramine Norpramin™
Digoxin Lanoxin™
Dicyclomine Bentyl™
Dipyridamole Persantine™
Dimenhydrinate Dramamine™, others
Disopyramide Norpace™
Diphenhydramine Benadryl™, others
Fentanyl Duragesic™, Actiq™
Doxepin Sinequan™
Furosemide Lasix ™
Doxylamine Unisom™, others
Fluvoxamine Luvox™
Fesoterodine Toviaz™
Haloperidol Haldol™
Flavoxate Urispas™
Hydralazine Apresoline™
Hydroxyzine Atarax ™, Vistaril™
Hydrocortisone Cortef™, Cortaid™
Hyoscyamine Anaspaz™, Levsin ™
lloperidone Fanapt ™
Imipramine Tofranil ™
Isosorbide Isordil™, Ismo™
Meclizine Antivert™
Levocetirizine Xyzal™
Methocarbamol Robaxin™
Loperamide Immodium™, others
Nortriptyline Pamelor™
Loratadine Claritin™
Olanzapine Zyprexa™
Metoprolol Lopressor , Toprol™
Orphenadrine Norflex™
Morphine MS Contin™, Avinza ™
Oxybutynin Ditropan™
Nifedipine Procardia™, Adalat™
Paroxetine Paxil™
Paliperidone Invega™
Perphenazine Trilafon™
Prednisone Deltasone™, Sterapred™
Promethazine Phenergan™
Quinidine Quinaglute™
Propantheline Pro-Banthine™
Ranitidine Zantac™
Propiverine Detrunorm™
Risperidone Risperdal ™
Quetiapine Seroquel™
Theophylline Theodur™, Uniphyl™
Scopolamine TransdermScop™
Trazodone Desyrel™
Solifenacin Vesicare™
Triamterene Dyrenium™
Thioridazine Mellaril™
Venlafaxine Effexor™
Tolterodine Detrol™
Warfarin Coumadin™
Trifluoperazine Stelazine™
Table 2: Anticholinergic burden scale drugs with ACB score of 2. Trihexyphenidyl Artane™
Generic Name Brand Name Trimipramine Surmontil ™
Amantadine Symmetrel™ Trospium Sanctura™
Belladonna Multiple This study was conducted at J. W. Ruby Memorial Hospital which
Carbamazepine Tegretol™ is located in Morgantown, West Virginia. This hospital is a tertiary
Cyclobenzaprine Flexerilm™ care academic hospital with 690 beds which serves as a statewide as
well as regional referral center for Pennsylvania, Maryland, and Ohio.
Cyproheptadine Periactin™
West Virginia is second in the nation for its aging population with
Loxapine Loxitane™
only Florida having a larger population greater than 65 years old. By
Meperidine Demerol™
2056, the population greater than 65 years old in the US is expected
Methotrimeprazine Levoprome™

Volume 5 • Issue 4 • 100116 • Page 2 of 5 •

 Citation: Brook e S, Dhar R, Bibb M, Hamed H, Navia RO, et al. (2021) Anticholinergic Burden and Hospital Delirium in an Appalachian University Hospital.
J Aging Geriatr Med 5:4.

to exceed those less than 17 years old [20]. This change is expected illustrates this comparison. The mean ACB score among delirium
to occur much earlier in West Virginia’s population and is projected negative patients was 2.08 while the mean ACB score for delirium
to occur by 2029. As of 2013, the Department of Health and Human positive patients was 2.23.
Resources in WV reported that 1 in 3 households had an adult greater Table 4: Anticholinergic burden score (ACB) scores on date of the
than 65 years old. Concurrently, West Virginia has a higher prevalence confusion assessment method (CAM).
of both disability and chronic diseases than the national averages Presence of
[20]. This population represents an early representation of the aging Number of
Delirium per Median 95% CI p-value
patients (n)
population within the United States. With this, medical comorbidity CAM
and disability rates are high reflecting some of the sickest amongst the No 134 2.5 2, 3
aging population in the US. Yes 40 2.5 2, 3.5 0.855
Methods Demographic data was collected and included: mean age, gender,
number of days hospitalized before CAM test was performed,
This is aretrospective cross-sectional study, which included 174
total length of stay, and patient origin (Table 5). To determine the
patients aged 65 years or older who were admitted to J.W. Ruby
impact of possible confounding variables, several potential risk
Memorial Hospital in West Virginia between October 15, 2018
factors were compared between groups. Those variables included
and March 21, 2019. Informed consent was obtained at the time of
possible precipitating factors for serum anticholinergic activity such
admission prior to ad-ministration of the CAM. The inclusion criteria
as renal function as well as other known causes of delirium such as
for the study were patients over the age of 65 years old admitted to
infection, stroke/TIA, myocardial infarction, and illicit drug/alcohol
a medicine floor. The exclusion criteria included those patients
intoxication. Neither was overrepresented with any one potential
undergoing detoxification for substance abuse, prisoners, comatose,
precipitating variable (Table 6).
actively dying, and lack of CAM documentation by the bedside nurse.
Patients were chosen as part of a previous study conducted at this Table 5: Sociodemographic characteristics of patients stratified based
on presence of delirium per Confusion Assessment Method (CAM).
hospital assessing inpatient delirium and CAM scores.
Characteristic (-) Delirium (+) Delirium p-value
The patients were assessed for delirium with the CAM upon Number of patients 134 40 1
arriving to a regular medicine floor regardless of whether they showed Age (years; mean ± SD) 75.77 ± 7.625 73 ± 7.31 0.574
delirium symptoms. Patient electronic medical records were reviewed Female (%) 55% 46% 0.469
for age, principal diagnoses, inpatient medications on date of CAM,
Number of
chronic diseases, kidney and liver function tests, and additional dayshospitalizedbefore 2.4 2.8 0.731
contributing factors for delirium. date of CAM (mean)
Total length of stay 5.62 6.81 0.773
Subjects were divided into delirium-positive and delirium-
negative groups based on the results of the CAM. Using the most Patient originprior to
0.362
CAM
current medication list from the date of the CAM, a cumulative ACB
Anotherinpatientward 34.30% 41.50%
score was derived.
Home 43.30% 36.60%
The primary endpoint was to determine the ACB score amongst Skilled nursing facility 3.00% 7.30%
both delirium positive and delirium negative patients. A clinically Outsidehospital 19.40% 12.20%
significant ACB score was defined as greater than three. The percentage Table 6: Potential confounding variables.
of delirium positive patients with a clinically significant ACB score was
compared to delirium negative patients with a clinically significant Variables (-) Delirium (+) Delirium p-value
ACB score. Numerical data was used for ACB score means rather than 23.91 ±
BUN (mean ± stddev) 23.90 ± 14.65 0.997
positive or negative ACB score because many patients were noted to 16.07
have ACB scores ranging between 2-4 and the difference was better Creatinine 1.48 ± 1.23 1.45 ± 1.05 0.905
reflected by numerical averages rather than categorical assessment. Total Bilirubin 182% 165% 0.871
Conjugated Bilirubin 1.028 0.873 0.774
A subsequent analysis compared ACB score on the date of the Albumin 2.77 ± 0.83 3.00 ± 0.83 0.213
CAM administration versus ACB score on the date of discharge.
AST 58.56 42.15 0.271
In this dataset, five patients died before discharge and were thus
ALT 5189.00% 6785.00% 0.551
excluded. Differences in ACB scores were compared with the Mann-
Alkaline Phosphatase 14939.00% 11254.00% 0.106
Whitney U test. Reported medians and non-parametric confidence
intervals were generated in R Hodges-Lehmann estimator. Urine Drug Screen 2.24% 2.50% 0.923
Benzodiazepine within 48
8.96% 12.50% 0.508
We hypothesized that if a patient was positive for delirium by hours of CAM
CAM, then they would have a significant anticholinergic burden Opioids within 48 hours of
0.2761 0.325 0.549
(ACB>3). Additionally, we hypothesized that the anticholinergic CAM
burden would have been reduced at the time of discharge. Recent Stroke/TIA 0.0373 0.1 0.116
Recent Surgery 0.1716 0.175 0.961
Results
Recent Heart Attack 0.0522 0.075 0.587
The data suggested no difference in ACB score between Active Infection 0.4701 0.45 0.823
patients with and without delirium (p=0.855) at the time of CAM Underlying Dementia 0.1716 0.075 0.132
administration. ACB scores ranged from 0-11, with roughly 75.3%
of patients on at least one anticholinergic medication. (Table 4)

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Citation: Brook e S, Dhar R, Bibb M, Hamed H, Navia RO, et al. (2021) Anticholinergic Burden and Hospital Delirium in an Appalachian University Hospital.
J Aging Geriatr Med 5:4.
Additionally, an ACB score was calculated at the time of discharge
for comparison to the day of CAM administration. This was completed
to assess if the anticholinergic burden had been reduced at the time
of discharge. Tables 5 and 6 illustrate these results. Patients who were
delirium-positive and had not died before discharge totaled 36. In this
group, the mean ACB on the date the CAM was 2.23, while the mean
ACB score on the date of discharge was 2.50. There was no statistically
significant change in ACB score by the date of discharge (p=0.738).
Discussion
Results from our study did not show an association between
anticholinergic cognitive burden and the diagnosis of delirium.
Delirium often has multiple precipitating factors and rendering an
obvious solitary association is difficult to ascertain. The ACB scoring
system was devised as a tool to help with accounting for anticholinergic
effects of certain commonly used pharmaceutical agents. However,
our study suggests that application of the tool would not benefit in
guiding identification of the cause of delirium nor justify the reduction
of a patient’s anticholinergic medications to treat their delirium.
Critiques of using drug scales are that the cumulative exposure to
anticholinergic medications are oversimplified into linear additive
models and these scales do not necessarily consider the underlying
patient characteristics including differences in pharmacodynamics,
cholinergic reserve, and endogenous anticholinergic activity [21].
Within this population, comorbidity alone may present a
unique challenge to identifying anticholinergic burden as a factor
contributing to the presence of delirium. In reviewing the data, it was
noted that many patients automatically scored higher on their ACB
score based on their comorbidities. For example, many patients with
diagnosed heart failure automatically had a score of two due to use
of both metoprolol as well as furosemide. Additionally, digoxin and
hydralazine were commonly present on their medication lists and will
also raise the score. The degree of multimorbidity in this population
may make it difficult to analyze a solitary contributing factor to the
presence of delirium. West Virginia ranks third in the nation by
definition for multiple chronic medical conditions. Multiple chronic
conditions are defined as two or more of the following group (arthritis,
asthma, cancer, COPD, coronary heart disease, diabetes, hepatitis,
hypertension, stroke or weak or failing kidneys). This population
notably does not reflect significant ethnic diversity as the 2013 WV
DHHR data indicates the state is 96.7% Caucasian [20].
Additional limitations of this study include the small sample
size of patients that were diagnosed with delirium. Forty patients
who were diagnosed with delirium out of 174 total patient electronic
medical records analyzed composes roughly 23% of the entire sample.
The small sample size lead to a lower powered study and it is possible
that a larger sample size would yield different results. Additionally,
the small sample size made stratification for analyzing confounding
variables challenging as there were not a sufficient number of patients
with delirium to investigate other effects. Also, the anticholinergic
usage was detected using medication orders rather than actual
dispensing data, which could inform about whether the exposure was
relatively new or cumulative over a prolonged period of time.
One more complexity of this study that differs from other studies
is that no cutoff for anticholinergic burden was selected, but rather the
ACB scores were treated as a continuous numerical variable. Research
groups that put an absolute cutoff for maximum anticholinergic value
showed significant associations between anticholinergic burden and
delirium. For example, Pascina and colleagues showed in 2012 a
Volume 5 • Issue 4 • 100116
relationship between ACB scores and Short Blessed Test (SBT), which
had previously been validated against the Mini-Mental State Exam
(MMSE) by Carpenter et al in 2011 [22,23].
Future directions for similar studies ought to significantly increase
sample size to better represent the population. Analysis of the ADS
and ARS may prove to have different outcomes for example.
Conclusion
The growing population of elderly patients may necessitate refined
tools for quick and early diagnosis of acute mental changes including
those potentially caused by the anticholinergic effects of common
medications. It is important to identify the acute negative impact that
polypharmacy has on the aging brain especially amongst an aging and
medically complex population. Therefore, there is value in identifying
tools that allow clinicians to quickly determine whether an acutely
delirious patient may benefit from reducing anticholinergic burden.
The relationship between delirium, anticholinergic burden scores,
and acetylcholine levels or serum anti-cholinergic levels should be
investigated further. More studies are thus needed to identify such
tools as well as establish therapeutic guidelines in dealing with
delirium. Therefore, evidence-based tools such as the ACB need
continued validation in order to reliably change practice.
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J Aging Geriatr Med 5:4.
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Author Affiliation Top
Department of Medicine, West Virginia University, Morgantown, WV, United
States.
2Department of Surgery, School of Medicine, West Virginia University,
Morgantown, WV, United States.
3Department of Civil Engineering, West Virginia University, United States.
4Department of Medicine, West Virginia University, Morgantown, WV, United
States.
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